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Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

ABSTRACT: Anemia protocols for hemodialysis patients usually titrate erythropoietin (ESA) according to hemoglobin and iron according to a threshold of ferritin, with variable response seen. A universally optimum threshold for ferritin may be incorrect, and another view is that ESA and iron are alternative anemia treatments, which should be selected based on the likely response to each. Hemodialysis patients developing moderate anemia were randomised to treatment with either an increase in ESA or a course of intravenous iron. Over 2423 patient-months in 197 patients, there were 133 anemia episodes with randomized treatment. Treatment failure was seen in 20/66 patients treated with ESA and 20/67 patients treated with iron (30.3 vs. 29.9%, p = 1.0). Successful ESA treatment was associated with lower C-reactive protein (13.5 vs. 28.6 mg/L, p = 0.038) and lower previous ESA dose (6621 vs. 9273 μg/week, p = 0.097). Successful iron treatment was associated with lower reticulocyte hemoglobin (33.8 vs. 35.5 pg, p = 0.047), lower hepcidin (91.4 vs. 131.0 μg/ml, p = 0.021), and higher C-reactive protein (29.5 vs. 12.6 mg/L, p = 0.085). A four-variable iron preference score was developed to indicate the more favorable treatment, which in a retrospective analysis reduced treatment failure to 17%. Increased ESA and iron are equally effective, though treatment failure occurs in almost 30%. Baseline variables including hepcidin can predict treatment response, and a four-variable score shows promise in allowing directed treatment with improved response rates.

SUBMITTER: Hildebrand S

PROVIDER: S-EPMC9796788 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

Hildebrand Sarah S Busbridge Mark M Duncan Neill D ND Tam Frederick W K FWK Ashby Damien R DR

Hemodialysis international. International Symposium on Home Hemodialysis 20220714 4

Anemia protocols for hemodialysis patients usually titrate erythropoietin (ESA) according to hemoglobin and iron according to a threshold of ferritin, with variable response seen. A universally optimum threshold for ferritin may be incorrect, and another view is that ESA and iron are alternative anemia treatments, which should be selected based on the likely response to each. Hemodialysis patients developing moderate anemia were randomised to treatment with either an increase in ESA or a course ...[more]

PMID: 35833334

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Project description:PurposeErythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL).Materials and methodsThe present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL.ResultsThere was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated.ConclusionIn cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

Project description:AimTo determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin.MethodsWe performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose.ResultsWith adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016).ConclusionsIn patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure.Clinical trial registrationClinicalTrials.gov Identifier for T1 trial: NCT00322413.

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Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

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Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

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